All that Glitters: How to start a contrast enhanced mammography program Caitlin Ward, Resident Physician, MSc, MD Anat Kornecki, Associate Professor, Women’s imaging, MD Western University, London Ontario St Joseph’s Healthcare, London Ontario London Health Sciences Centre, London Ontario

Disclosure of conflict of interest Presenter Disclosure Speaker Name: Caitlin Ward I have no relationships with commercial interests or conflicts of interest to disclose

Background Contrast enhanced spectral mammography (CESM) is a relatively new imaging technique Made possible by the advent of digital mammography Developed in the early 2000s and refined and validated over the past decade Combines conventional digital diagnostic mammography with the administration of iodinated Administration of iodinated contrast increases the ability to detect malignant breast lesions as a result of the increased neoangiogenesis present in malignant tissue

CESM uses CESM is not currently a part of the BiRADS breast assessment program There is no BiRADS lexicon for use in CESM, the mammography and MRI lexicon and assessment categories are applied CESM is therefore currently used as an adjunct breast imaging method in the “post screening” population

When is CESM helpful? CESM is primarily used as a problem solving tool: For assessing mammographically equivocal lesions To assess mammographically suspicious lesions with no ultrasound correlate To reassure benignity in BiRADS 3 lesions and/or avoidance of biopsy It can also be used as part of breast cancer staging: Detection of concurrent ipsilateral cancers/multifocality/multicentricity Suspicion of axillary lymph node involvement It is an alternative method of assessing for neoangiogenesis and increased probability of malignancy in patients for whom MRI is contraindicated or unavailable: Claustrophobia Contraindication to gadolinium Ferromagnetic foreign body

Technique Current CESM uses a dual energy technique, taking advantage of the K-edge of iodine (33.2 keV). A copper filter is used to tailor x-rays to a spectrum compatible with the K-edge of iodine Iodinated contrast is injected at a dose of 1.5 ml/kg body weight and a rate of 3 ml/s Image acquisition begins at 2 minutes post contrast administration Two image sets are acquired in routine mammographic views (MLO and CC) of each breast Low energy (standard digital mammogram) at 26 - 32 kVp High energy at 45 - 49 kVp Software recombination generates a set of low energy routine mammographic views and views with background breast tissue subtracted, demonstrating only contrast enhancement Dromain et al 2009

CESM performance Multiple studies have demonstrated that CESM has a specificity similar to conventional digital mammography: 56+ % Non-malignant lesions may also enhance, accounting for low specificity Fibroadenoma Papilloma Radial scar Comparable sensitivity to MRI (no significant difference in multiple studies): 93 – 98%% Dromain et al 2011, Fallenberg et al 2014, Lee-Felker et al 2017, Tagliafico et al 2016

Other CESM advantages Increased patient convenience: Can be booked same day as assessment mammogram and ultrasound, preventing second appointment Short appointment times: Approximately 15 minute exam time Shorter time to complete assessment May be completed in a single day Since it can be done same day, full assessment can be completed by a single radiologist Increased patient comfort in comparison to MRI Due to positioning, exam time, shorter breast compression time Avoidance of gadolinium usage (lifetime gadolinium accumulation) As the second set of images acquired are high dose, relatively low increase in overall glandular dose: 1.2 - 1.5 x conventional digital mammography More cost effective than MRI

Disadvantages/shortcomings of CESM Increased radiation dose Currently no method of performing biopsy under CESM guidance, although this is under development in research phases In comparison to MRI, field of view is limited and axillae and deep chest wall not adequately assessed for staging purposes Currently no BiRADS lexicon

How to implement a CESM program Hardware/software requirements New equipment Personnel training Safety protocols Scheduling Interpretation

Hardware/Software requirements and equipment GE Healthcare SenoBrightTM system Dual energy acquisition Addition of a copper filter Calculation algorithm for production of recombined images Contrast power-injector to achieve adequate rate of injection and optimal tissue contrast

Our contrast mammography room with control panel

Personnel training Patient positioning: Efficiency and consistency necessary Timing is of crucial importance in image acquisition as peak enhancement occurs between 5-7 minutes, with washout after 10 minutes Technician training How to insert an IV catheter Use of a power injector

Development of protocols Many protocols were “borrowed“ from the CT program at our institution: Consent for contrast administration Safety protocols for contrast reactions Calculation of iodinated contrast dose Exam protocols for contrast administration and timing of image acquisition

Calculation of contrast dose

Scheduling Troubleshooting was required in the early days of the program to determine optimal scheduling, including: Length of appointment time Staffing requirements Number of staff Training requirements Physician presence Required number of add-on appointments per day

Interpretation Phyician training Breast imagers involved in interpretation of CESM studies completed a CME course on CESM interpretation Training and site visits from GE Healthcare and with the Gustav Roussy Centre in Paris, France BiRADS As no lexicon currently exists, the lexicons develped for digital mammography and MRI are used as appropriate Report generation CESM exams are reported in conjunction with ultrasound and digital mammography studies performed as part of the same assessment

Case examples

Case 1: Invasive mammary carcinoma with lobular features Distortion within the right lower outer quadrant on screening mammogram: a,b. Right CC and MLO views show distortion. c,d. Right CC and MLO CESM views show avid enhancement of the distortion, suspicious for malignancy.

Case 2: Abscess New palpable abnormality. a,b. Right CC and LM views show a 2.5 cm ill definited mass in the upper outer quadrant. c,d. Right CC and LM CESM views show avid peripheral enhancement with multiple surrounding smaller enhancing masses.

Case 2: Abscess ultrasound images New palpable abnormality. e,f. Ultrasound with (e) and without (f) colour Doppler demonstrate a complicated cyst.

Case 3: Phylloides tumour Palpable left upper outer quadrant lump with rapid increase in size. a,b. Left XCCL and MLO views show a heterogeneous mass in the upper outer quadrant. c,d. Left XCCL and MLO CESM views show heterogeneous nodular enhancement.

Case 3: Phylloides tumour ultrasound image Palpable left upper outer quadrant lump with rapid increase in size. e. Ultrasound shows a mixed solid and cystic mass.

Case 4: Inflammatory cyst Incidental finding on work up for a contralateral asymmetry. a,b. Left CC and MLO views show a well circumscribed mass in the upper outer quadrant. c,d. Left CC and MLO CESM views show peripheral enhancement and central lucency.

Case 5: Satellite lesions in invasive mammary carcinoma Palpable lump in left upper outer quadrant with scattered background parenchyma. a,b. Left CC and MLO views show an ill-defined density with associated calcifications. c,d. Left CC and MLO CESM views show avid enhancement of a 3 cm mass with multiple additional enhancing satellite lesions.

Case 6: Benign cysts Multiple asymmetries within the right breast on screening mammogram: a,b. Right CC and MLO views show asymmetries. c,d. Right CC and MLO CESM views no enhancement, supportive of benignity.

Conclusion Contrast enhanced mammography has been a valuable addition to the breast imaging practice at our institution Relatively smooth implementation with many protocols borrowed from our CT practice Improved patient care with decreased time to work up completion and increased convenience

References Chou, C. P., Lewin, J. M., Chiang, C. L., Hung, B. H., Yang, T. L., Huang, J. S., Liao, J. B. & Pan, H. B.. 2015. Clinical evaluation of contrast-enhanced digital mammography and contrast enhanced tomosynthesis--Comparison to contrast-enhanced breast MRI. Eur J Radiol 84: 2501-2508. doi: 10.1016/j.ejrad.2015.09.019. Dromain, C., Balleyguier, C., Adler, G., Garbay, J. R. & Delaloge, S.. 2009. Contrast-enhanced digital mammography. Eur J Radiol 69: 34-42. doi: 10.1016/j.ejrad.2008.07.035. Dromain, C., Thibault, F., Muller, S., Rimareix, F., Delaloge, S., Tardivon, A. & Balleyguier, C.. 2011. Dual-energy contrast-enhanced digital mammography: initial clinical results. Eur Radiol 21: 565-74. doi: 10.1007/s00330-010-1944-y. Fallenber, E.M., Dromain, C., Engelken, F., Krohn, M., Sing, J.M., Ingold-Heppner, B., Winzer, K.J., Bick, U., Renz, D.M.. 2014. Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size. Breast 24:256-264, doi:10.1007/s0033-013-3007-7. Fallenberg, E. M., Schmitzberger, F. F., Amer, H., Ingold-Heppner, B., Balleyguier, C., Diekmann, F., Engelken, F., Mann, R. M., Renz, D. M., Bick, U., Hamm, B. & Dromain, C.. 2017. Contrast-enhanced spectral mammography vs. mammography and MRI - clinical performance in a multi-reader evaluation. Eur Radiol 27: 2752-2764. doi: 10.1007/s00330-016-4650-6. Lee-Felker, S. A., Tekchandani, L., Thomas, M., Gupta, E., Andrews-Tang, D., Roth, A., Sayre, J. & Rahbar, G.. 2017. Newly Diagnosed Breast Cancer: Comparison of Contrast-enhanced Spectral Mammography and Breast MR Imaging in the Evaluation of Extent of Disease. Radiology 285: 389-400. doi: 10.1148/radiol.2017161592. Tagliafico, A. S., Bignotti, B., Rossi, F., Signori, A., Sormani, M. P., Valdora, F., Calabrese, M. & Houssami, N.. 2016. Diagnostic performance of contrast-enhanced spectral mammography: Systematic review and meta-analysis. Breast 28: 13-19. doi: 10.1016/j.breast.2016.04.008. Tardivel, A. M., Balleyguier, C., Dunant, A., Delaloge, S., Mazouni, C., Mathieu, M. C. & Dromain, C.. 2016. Added Value of Contrast-Enhanced Spectral Mammography in Postscreening Assessment. Breast J 22: 520-528. doi: 10.1111/tbj.12627.  Thibault, F., Balleyguier, C., Tardivon, A. & Dromain, C.. 2012. Contrast enhanced spectral mammography: better than MRI?. Eur J Radiol 81 Suppl 1: S162-4. doi: 10.1016/s0720-048x(12)70068-2.